The broad goal of the proposal is to understand the functional organization of the early thalamocortical stages of processing in the auditory system. This involves a better functional understanding of the various pathways connecting the medial geniculate body (MGB) plus first and second auditory cortices (A1 and A2). We will use an in vitro slice preparation of the mouse brain in which different slice configurations will have the MGB to A1/A2, A1 to MGB, and A1 to A2 pathways intact. We will use uncaging of glutamate by photostimulation or minimal electrical stimulation to test the function of each of these glutamatergic pathways, and this will be complemented by the use of channelrhodopsin methodology. In particular, we shall attempt to classify each pathway as Class 1 (i.e., formerly driver), Class 2 (formerly modulator), or other, and thereby we hope to construct a functional hierarchy of information flow. We shall also test the role of layer 6 corticothalamic cells in gating thalamocortical transmission and test the complex hypothesis, first, that there exists parallel direct and corticothalamocortical pathways linking A1 with A2, and second, that these dual pathways operate in a coincidence detection manner to control information flow. This could also provide more general insights regarding cortical functioning, particularly with respect to new evidence that different cortical areas can dynamically cooperate depending on behavioral needs. PUBLIC HEALTH RELEVANCE: We must better understand auditory information flow through the first few stages of cortical processing to begin to understand how pathology in these pathways leads to hearing loss including defects in cognitive auditory functions, such as lexical-semantic processing, phonological information extraction, selective attention and object recognition.